Determining the Cause and Severity of Sepsis with a Point-of-Care Test

Episode Summary

Executive Summary: The interview explains how sepsis is now understood as a dysregulated immune response to infection, not simply a bloodstream infection, and why that makes diagnosis and treatment so difficult. Inflammatics’ FDA-cleared Triverity test uses 29 mRNA markers and AI to rapidly classify bacterial vs. viral infection and predict illness severity, aiming to improve ER triage, reduce missed infections, and identify patients who need ICU-level care or broader workups.

Main Topics: Modern Understanding of Sepsis (Priority: 5/5): Tim Sweeney describes sepsis as infection plus an abnormal host immune response that can continue damaging the body even after the pathogen is controlled, moving the definition away from the older idea of 'blood poisoning.' Clinical and Economic Burden (Priority: 5/5): The discussion emphasizes sepsis as a major healthcare crisis because it is expensive, often misdiagnosed, and associated with high mortality and malpractice risk. Limitations of Current Diagnosis and Treatment (Priority: 5/5): Sweeney explains that clinicians still rely heavily on guesswork and broad protocols, with many infections not definitively identified by standard microbiology and no approved therapy that directly treats the immune dysfunction of sepsis. Triverity Test and ER Triage (Priority: 5/5): Inflammatics’ Triverity system provides rapid bacterial, viral, and illness-severity scores from a blood sample, helping emergency physicians decide on antibiotics, hospitalization, and further workup. Sepsis Subtyping and Precision Medicine (Priority: 4/5): The interview highlights efforts to classify sepsis into molecular subtypes/endotypes so that future immunomodulatory therapies can be matched to patients more effectively, similar to cancer subtyping. Technology Platform and Data Science (Priority: 4/5): Sweeney discusses the company’s AI/machine-learning model built from 29 host mRNA targets and a large, heterogeneous dataset, as well as the platform’s broader potential for new blood tests beyond sepsis. Company Strategy and Future Applications (Priority: 3/5): Inflammatics plans to scale Triverity adoption while leveraging the same reader/cartridge platform for additional diagnostics in infections, critical illness, and possibly cardiac care.

Key Arguments: Sepsis should be understood as an infection-driven immune dysregulation, not merely a bloodstream infection. Early identification of bacterial vs. viral vs. noninfectious illness is essential because standard clinical judgment and microbiology often miss cases or lead to overtreatment. Current sepsis care improves survival but still cannot address the underlying inflammatory syndrome, which is why mortality remains substantial. One reason sepsis drugs have failed is that sepsis is not one disease; it likely contains multiple biologically distinct subtypes requiring different therapies. Triverity can add value at triage by identifying hidden bacterial infections, unnecessary antibiotic use, and patients who appear less sick than they are. A single underlying testing platform can support many future assays by swapping target panels rather than rebuilding hardware. Precision diagnostics could eventually support personalized treatment in critical care, similar to biomarker-driven oncology. Inflammatics’ large, diverse training set and AI approach were necessary to build a test robust across different patient populations and clinical settings.

Data Points: Medicare spending on sepsis: $53 billion - Estimated annual Medicare spending attributed to sepsis diagnoses Diagnostic trials failed: More than 100 - Number of drug trials that have not produced an approved therapy that directly treats sepsis immune dysfunction Sepsis mortality reduction: From about 30-40% to about 20% - Sweeney said modern protocolized care reduced mortality, but rates remain high Emergency department visits in the U.S.: About 140 million per year - Approximate annual ED volume used to frame the diagnostic funnel Suspected infection ED visits: 30-40 million per year - Subset of ED visits where infection is suspected Sepsis cases per year: 1-2 million - Approximate annual sepsis incidence in the U.S. Sepsis share of suspected infection cases: About 5% - Sepsis represents a small fraction of suspected infection presentations Triverity turnaround time: 30 minutes - Time from blood sample to test result Biomarkers measured: 29 host immune mRNAs - Panel used by the Triverity AI model Training dataset size: About 20,000 patients - Patient records used to train the algorithm Clinical settings in dataset: More than 50 settings - Heterogeneous sources included in model development Clinical studies in dataset: Nearing 100 studies - Scale of the evidence base used for training/validation Missed bacterial pneumonia rate by microbiology: About 60% missed - Standard microbiology can fail to detect deep-seated bacterial pneumonias Observed missed bacterial infection at discharge: One in eight - In a 1,200-patient study of patients with cough and fever, this share left the ED without antibiotics despite later bacterial diagnosis Large study size: 1,200 patients - Study used for FDA clearance and accuracy evaluation DARPA funding: $1 million - Early funding used to launch the company Company launch year: 2017 - Sweeney said he went full time to found Inflammatics in 2017 Nature Medicine subtype finding: Four subtypes - Critical illness/sepsis subtypes described using lymphoid and myeloid axes

Pivotal Quotes: "Sepsis is the combination of an infection anywhere in the body combined with a quote dysregulated host response." — Tim Sweeney: Defines the modern concept of sepsis beyond bloodstream infection "There are zero approved therapies that actually treat the underlying immune response of sepsis." — Tim Sweeney: Explaining why current ICU care addresses complications rather than the root cause "For the first time, based on our immune profiling, within 30 minutes, we can tell who has a bacterial infection, separately who has a viral infection." — Tim Sweeney: Describing Triverity’s core clinical capability

Implications: If adopted widely, rapid host-response testing could improve triage, reduce unnecessary antibiotics and admissions, and identify high-risk patients earlier. Longer term, sepsis care may shift toward subtype-specific, precision immunotherapy.